It is proposed to study the biochemical basis for the finding, made in this laboratory, that the semi-synthetic nucleoside analogue, aminonucleoside of puromycin (AMS), has profoundly different effects on the kinetics of proliferation of normal versus transformed human cells. This will be done by extending current studies which are designed to identify and characterize the alterations in control mechanisms in transformed cells responsible for these differences. The information thus obtained may permit an entirely new approach to the chemotherapy of cancer. Aminonucleoside arrests the cell progress of diploid fibroblasts under conditions which allow continued growth of their transformed counterparts, and is known to inhibit selectively polyadenylation of messenger RNA in normal fibroblasts, but in transformed cells it principally inhibits ribosomal RNA production. Understanding of the basis for these differences may provide important clues to the nature of alterations in the overall control mechanisms which characterize neoplastic cells generally, and thus expose them to a more effective chemotherapeutic attack. It is also planned to optimize conditions for selective killing of transformed cells by S-phase specific cytotoxic drugs in mixed cultures of normal and transformed cells, by protection of normal cells with aminonucleoside or analoques.